Furin is a member of the family of subtilisin/kexin-like proprotein convertases (PCs) that process protein at basic residues. This protein is produced as a 104 kDa zymogen that is converted into a 98 kDa mature following autocatalytic cleavage at two sites. The cleavages occur during enzyme progression from the endoplasmic reticulum to the trans golgi network (TGN).

Expression

Expression of Furin in different tissues was localized by northern blot, in situ hybridization and histochemistry. These analyses demonstrated that Furin is ubiquitously expressed. However, high expression of Furin was found in liver and spleen.

The Furin catalytic domain has a high percentage of homology with those of the other PCs which range from 70% (between PACE4 and Furin) to 54% (between PC2 and Furin).

Implicated in

Note

Entity

Cancer

Note

To date Furin is expressed in all tissues and cell lines examined so far but at very low levels as compared to tumor cells and tissues. Inhibition of Furin activity or expression in tumor cells reduced dramatically their malignant phenotype (proliferation, invasion, migration...) and their ability to induce tumor growth.

A comparative study of the Furin expression between normal human ovarian surface epithelium and cancer cell lines as well as ovarian epithelial cancer specimens revealed that Furin is only expressed in cancer cell lines especially in primary tumors from patients whose life expectancy don't exceed five years.

Entity

Oral tongue squamous cell carcinoma

Note

The Furin expression was found to be correlated with the grade of oral tongue squamous carcinoma. The highest Furin expression was found in the most aggressive line of squamous cell carcinoma (SCC) and the least Furin expression in the less aggressive line.

The involvement of Furin in bacterial infections was suggested by its capacity to activate the various classes of bacterial toxins such as the Diphteria toxin, Pseudomonas Aerugenosa exotoxin A, Botulinum neurotoxin, Bordetella dermonecrotic toxin, Anthrax and aerolysin.

Entity

Neurodegenerative pathology

Note

Furin can activate the α and β-secretase which are implicated in the cleavage of amyloid-β the principal component of senile plaques.

The proteolytic processing of pro-platelet-derived growth factor-A at RRKR(86) by members of the proprotein convertase family is functionally correlated to platelet-derived growth factor-A-induced functions and tumorigenicity.

Mutation of the f-protein cleavage site of avian paramyxovirus type 7 results in furin cleavage, fusion promotion, and increased replication in vitro but not increased replication, tissue tropism, or virulence in chickens.